This is the competing renewal of R01-AG-21665 to continue and extend a study of physical functioning and osteoarthritis in age-eligible women, begun as a Michigan site-specific study to the Study of Women Across the Nation (SWAN), the multi-centered, community-based study of women at the mid-life with a focus on menopause. National health surveys have identified that 15% of persons aged 45-64 had some functional limitation or disability. Of those, 50% of persons identified that the functional limitation or disability developed between the ages of 40-55 years. However, relatively little attention has been directed understanding the development of functional limitations (which probably begins for many women in mid-life) and their relation to the development of chronic diseases. The initial aims were to longitudinally characterize elements of physical functioning in 543 (baseline) mid-aged African American and Caucasian women during the menopausal transition where participation at the 8th annual follow-up in 2005 was 85%. We now propose an extension of this SWAN site-specific study. This competing renewal application includes the following measures: a) leg strength, gait analyses, timed measures of sit-to-rise, functional reach, timed stair climb, timed 40 feet walk and grip/pinch strength measures, b) objective measures of osteoarthritis including x-ray and MRI, c) the SF-36 physical functioning scale as well as other arthritis-based functioning measures, d) measures of body composition (fat and lean mass), body topology, and measures of hs C-reactive protein and urinary isoprostanes. Hypotheses include: a) Fat mass level and its change are more likely to be associated with the inflammatory responses at the joints leading to functional decline whereas lean mass or its change (sarcopenia) are more likely to be associated with roles of physical activity and strength in knee osteoarthritis and functional status; b) The magnitude of functional decline is greater among women when metabolic derangements accompany obesity as compared to women who are similarly obese but have minimal metabolic derangement; and c) Functional decline and the presence of osteoarthritis will increase when a shift in estrogen status with menopause leads to an alteration in the essential intermediate radicals for the cyclooxygenase mechanisms of inflammation. This is an important study because there is little research about the natural history of functional limitations in women aged 40-55, yet there are more women with functional limitations and disabilities than men. Among the elderly, older women live longer, develop more chronic disease and experience more prolonged and severe disability than older men. [unreadable] [unreadable] [unreadable] [unreadable]